α-Carbonic anhydrases are sulfatases with cyclic diol monosulfate esters

Figures & data

Scheme 1.  Reactions 1 and 2 catalyzed by α-carbonic anhydrases (CAs). Whereas the 4-nitrophenyl acetate hydrolysis occurs easily, the corresponding sulfate 2 is not a substrate for CAs^1–3.

Table 1.  K_I values obtained from regression analysis graphs for hCA I, hCA II, hCA IV, and hCA VI in the presence of different inhibitors concentrations (μM).

Inhibitor	hCA-I	hCA-II	hCA-IV	hCA-VI
4	41.3	2.13	13.7	93.1
5	163	4.08	23.6	116
6	77.2	5.41	16.3	123
7	188	8.27	53.8	145
8	32.7	10.4	199	221
9	142	23.7	234	278
10	135	4.68	18.8	76.2
11	423	32.4	77.9	127
Phenol (12)	10.2*	5.5*	9.5*	208*
Catechol (13)	4003*	9.9*	10.9*	606*
Resorcinol (14)	795*	7.7*	570*	550*
Acetazolamide	36.2	0.37	5.64	0.34

Mean from at least three determinations. Errors in the range of ±3% of the reported value (data not shown).

hCA, human carbonic anhydrase.

*From reference 13.

Figure 1.  Structure of compounds 10–14 and (AZA).

Scheme 2.  The hydrolysis reaction of compound 4, 6 and 8 with carbonic anhydrase II (CA II) isoenzyme.

Scheme 3.  The hydrolysis reaction of 2-Hydroxy-5-nitro-α-toluenesuIfonic acid sultone³ (3) and cyclic sulfate esters (4).

Table 2.  Time-% conversion rate with buffer or H₂O medium (rt, 1 atm).

Compound	Conversion rate
	15 min	30 min	45 min	60 min	90 min	120 min	150 min	180 min
4	0.5%	7%	35%	53%	67%	93%	97%	>99%
6	0	1%	11%	25%	34%	51%	73%	86%
8	0	0	0	0	0	<1%	1%	1%

Kaiser ET, Lo KW. The carbonic anhydrase catalyzed hydrolysis of 2-hydroxy-5-nitro-α-toluenesuIfonic acid sultone. J Am Chem Soc 1969;91:4912–4918.

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